Neuronal nicotinic acetylcholine receptors nAChRs

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

Rao, T. S., Correa, L. D., Reid, R. T., Lloyd, G. K. Evaluation of anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (nAChR) ligands in the rat tail-flick assay, Neuropharmacology 1996, 35, 393-405. 

Abstract The existence of neuronal nicotinic acetylcholine receptor (nAChRs) expression in the brain was discovered 30 years ago. Although the relevance of neuronal nAChRs at the time of their discovery was debated, it is now clear that nAChRs are expressed throughout the brain where they mainly serve a modulatory role. Neuronal nAChRs increasingly have become of interest due to the many observations that various nAChR subtypes exhibit abnormal expression or function in a wide assortment of neurological diseases. In this review, the putative role of nAChRs in brain disease is discussed in several broad categories (1) diseases associated with a loss of nAChRs, (2) diseases associated with innate differences in the expression of nAChRs, (3) diseases associated with genetic variability in genes that code for nAChR subunit proteins, and (4) diseases in which nAChRs are implicated based on the observation that nicotine has a therapeutic effect. 

Nicolotti, O., Pellegrini-Calace, M., Altomare, C., Carotti, A., Carrieri, A., and Sanz, F. 2002. Ligands of neuronal nicotinic acetylcholine receptor (nAChR) Inferences from the Hansch and 3-D quantitative structure-activity relationship... 

Nicotine is an agonist to the neuronal nicotinic acetylcholine receptors (nAChR). These receptors are the likely site at which nicotine exerts its central actions. Evidence supports the involvement of the central nAChR in neurotransmitter release (195), and a large body of evidence indicates that dopamine release from dopaminergic neurons is mediated by activation of the brain nAChRs (196). It has also been shown that both nicotinic receptors and muscarinic receptors in the ventral tegmental area (VTA) activate the dopaminergic neurons and thus play a role in the reward effect of nicotine (197). In addition, animal data sug-... 

The cholinergic system in insects is the main target of insecticides. One class of molecules, the neonicotinoids, induces direct activation of the neuronal nicotinic acetylcholine receptors (nAChRs). In the honey bee these receptors are mainly distributed in the olfactory pathways that link sensory neurons to antennal lobes and mushroom bodies. These structures seem to play an important role in olfactory conditioning. We have previously shown that cholinergic antagonists injected in different parts of the brain impaired the formation and retrieval of olfactory memory. We then advanced the hypothesis that, through the activation of the nAChR, the neonicotinoid imidacloprid (IMI) would lead to facilitation of the memory trace. 

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